AVEO Oncology announced The Oncologist has published a post-hoc analysis of long-term progression free survival, overall survival and safety data from the Phase 3 TIVO-3 trial evaluating FOTIVDA® (tivozanib) in patients with relapsed or refractory (R/R) advanced renal cell carcinoma (RCC). In the publication, FOTIVDA demonstrated a consistent safety profile and a long-term survival benefit in patients who were alive and progression-free at 12 months, suggesting a durable clinical benefit and safety across age groups regardless of prior treatment. TIVO-3 compared the efficacy and safety of the vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) FOTIVDA and sorafenib (Nexavar®) in patients with R/R advanced RCC whose disease progressed with two or three prior systemic therapies.

The trial included a predefined subgroup of patients (26%) who were previously treated with both an immuno-oncology (IO) therapy and a VEGFR TKI. The post hoc analysis showed investigator-assessed landmark long-term progression-free survival (PFS) rates were higher with FOTIVDA compared to sorafenib (3 years: 12.3% vs. 2.4%; 4 years: 7.6% vs.

0%). After 22.8 months mean follow-up, the overall survival (OS) hazard ratio (HR) for FOTIVDA was 0.89 (95% confidence interval [CI]: 0.70-1.14); when conditioned on a clinically meaningful 12-month PFS time point, FOTIVDA showed significant improvement in OS compared to sorafenib (HR: 0.45; 95% CI: 0.22-0.91; 2-sided P = 0.0221). Mean time on treatment was 11.0 months with FOTIVDA and 6.3 months with sorafenib.

There were fewer treatment-related adverse events (TRAEs) and lower dose modification rates with FOTIVDA than with sorafenib as well as fewer grade =3 TRAEs on FOTIVDA (46%) than sorafenib (55%). Dose modification rates were lower with FOTIVDA than with sorafenib across age and prior IO subgroups; and prior IO therapy did not impact dose reductions or discontinuations in either arm. The advent of targeted therapies and IO therapies is considered a major advancement in the treatment of RCC, and IO-based combination therapy is the frontline standard of care for patients with advanced RCC who require systemic therapy.4 However, despite the demonstrated benefits of IO combination therapies, most patients with RCC ultimately experience disease progression and require subsequent treatments5, underscoring the need for safe, tolerable and effective therapies in the refractory setting.